A retrospective analysis of 173 skin biopsy specimens of myeloid leukemia cutis (MLC) was performed to determine histologic and immunophenotypic criteria that could distinguish the varied myeloid disorders from one another. For the study, 11 relevant histologic items were scored and 12 antigens were studied (CD68 [KP1], CD163, CD14, CD4, myeloperoxidase [MPO], CD33, CD117, CD34, CD56, MIB-1, CD303, and CD123). Underlying myeloid disorders were essentially acute myeloid leukemias (65.3%), chronic myelomonocytic leukemias (11.0%), and refractory anemia (10.4%). Skin lesions were de novo in 7.5%, concurrent in 26.6%, and subsequent in 60.7%. Several morphologic characteristics (density, size of tumor cells, inflammatory background) were statistically useful in distinguishing between varied myeloid disorders. De novo MLCs displayed a specific morphologic profile. Association of CD68, CD33, and MPO could diagnose 100% of the cases of MLC. However, the immunohistochemical panel could not distinguish between the varied underlying myeloid disorders, with the exception that CD123 was particularly powerful in recognizing chronic myelomonocytic leukemia and also permitted reclassification of 4 cases as blastic plasmacytoid dendritic cell neoplasm.